Over the past decade, malaria deaths in Sub-Saharan Africa decreased nearly 40% primarily due to increased use of insecticides that target the Anopheles mosquito vector. However, both physiological and behavioral resistance in the mosquito population threatens the sustainability of current control efforts. In order to capitalize upon the success of the past decade, novel control techniques need to be integrated with more judicious use of insecticides. The sterile insect technique involves mass-rearing of male mosquitoes, which are then sterilized via irradiation and released into the wild to mate with females. While conceptually simple and successfully deployed in other insects, the sterile insect technique has not worked on African Anopheles primarily because irradiation reduces the overall fitness of males, making them poor competitors relative to wild type males. Our proposal aims to use a cutting-edge, combinatorial genomics approach to identify genes that are critical to male fertility, laying the foundation for creating male mosquitoes that are sterile, but otherwie normal. A majority of the important malaria vectors in Africa belong to the Anopheles gambiae complex, which consists of at least eight morphologically identical -- but genetically, behaviorally, and ecological distinct -- species. While the diversity of the Afrotropical vectorial system is normally regarded as an impediment to malaria control, we plan to use it to our advantage: classical studies showed that when two species within the An. gambiae complex are reciprocally crossed the F1 hybrid males are completely sterile. However, F1 hybrid females are fully fertile and can be backcrossed to generate recombinant male progeny that range from completely sterile to fully fertile, providing the foundation to connect genotype with phenotype. I the following grant, we plan to dissect the genetic basis of hybrid male sterility between the two vector species An. gambiae and An. merus. By combining high-throughput quantitative genomics with targeted trasncriptomics and publically-available population genetic data our approach will result in a select list of candidate sterility genes. Ultimately, our project aims to use the complexity of the African vectorial system against itself; identification of genes criticalto proper sperm development will enable new strategies for vector control through population suppression.